The overall objective of our research is to explain the behavior of the respiratory control system based on an understanding of the basic properties of and interactions among individual respiratory neurons. Thus we believe that the behavior of the respiratory system can be synthesized based on an understanding of individual neuronal elements and their interconnections. This proposal focuses on in vitro studies of an important class of respiratory motoneuron, the hypoglossal motoneuron. A specific goal of the research is to understand basic mechanisms responsible for the behavior of the motoneurons. The first specific aim is to continue our studies of membrane currents present in these motoneurons. By using voltage-clamping of hypoglossal motoneurons, with both conventional and patch-type microelectrodes in thick-and thin-medullary slices of rat, we will investigate three classes of membrane currents that are activated or de-inactivated by membrane hyperpolarization. These three include Ca2+ currents and channels, transient K+ currents and the mixed cationic inward rectifier current, Ih. These currents will be isolated to determine, in detail, their ionic bases, pharmacology, voltage-dependency and kinetics. The second specific aim is to investigate the direct effects on hypoglossal motoneurons of two neurotransmitters, serotonin (5-HT) and thyrotropin- releasing hormone (TRH). Specific membrane ionic and intracellular second- messenger mechanisms by which these transmitters act will be determined. The third specific aim is to use the rhythmically active in vitro neonatal brainstem spinal cord preparation, with voltage-clamp recording, to test the hypothesis that respiratory-related rhythmic activation of hypoglossal motoneurons is partly determined by voltage-and-time-dependent conductances. The results of these studies will provide fundamental information about the normal functioning of hypoglossal motoneurons. In addition, since hypoglossal motoneurons regulate the contraction of the tongue and this muscle determines in part patency of the upper airway, a comprehensive understanding of these motoneurons may be essential to our understanding of certain pathological states, such as obstructive sleep apnea and obstructive apnea of prematurity.